LIfT BioSciences has revealed preclinical data demonstrating that its immunomodulatory alpha neutrophil product (IMAN) showed potent killing of pancreatic cancer tumoroids.
The tumoroid originated from a patient with pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. The patient was unresponsive to conventional chemotherapy treatment with Abraxane (nab-paclitaxel), but initially responded positively to Gemzar (Gemcitabine), after which the tumor aggressively returned and stopped responding to either of the conventional chemotherapies.
For these patients, there are limited alternative options. Immune checkpoint inhibitors (ICIs) may help a small proportion of patients, but ultimately, chances of survival are less than 5%.
In the tumoroid model, a similar outcome was observed with paclitaxel having no cancer cell killing effect, whilst a single dose of gemcitabine resulted in destruction of the tumoroid. In comparison, a single dose of LIfT BioSciences’ IMAN resulted in potent destruction of the tumoroid.
Importantly, unlike paclitaxel and gemcitabine, which are fixed in their mechanism of actions, and with the initial effects of gemcitabine often not lasting as the cancer adapts, the resulting IMANs prevent the tumor from evading treatment by still recognizing tumor cells as they adapt (as exemplified by Hirschhorn and colleagues in last month’s Cell publication on how neutrophils eliminate tumor escape).
IMAN therapy benefits from not being dependent on just antigen recognition in tumors as, for example, a T-cell does. IMANs have multiple threat recognition and killing mechanisms, as well as the ability to recruit the rest of the immune system and help other immuno-oncology therapies, including ICIs, to attack solid tumors more effectively.
LIfT Biosciences moving toward clinical trials
Alex Blyth, chief executive officer of LIfT BioSciences, said: “After patenting our N-LIfT technology platform in 2016 to produce IMANs with the hope of creating a new way to destroy solid tumors, we continue to see our neutrophil based therapy successfully delivering against its promise as we move into clinic. These positive pre-clinical results in pancreatic cancer demonstrate the potential of our IMAN as an alternative and second line treatment option for patients who haven’t responded to currently available treatments.
“This is due to its unique ability to keeping killing cancer cells as they adapt and to recruit the patient’s immune system to give lasting immunity. We look forward to continuing to provide updates on LIfT Biosciences’ exciting research as we continue to work towards clinical trials starting in the first half of next year.”
IMANs have a unique dual mechanism of action as a cell therapy, where they both directly kill tumors and orchestrate the rest of the immune system to join the attack. This new direct killing data builds on previous data announced by LIfT BioSciences using PDAC biopsies, demonstrating that IMANs modify the tumor micro-environment (TME) and then activate patients own immune cells into attack mode, such as tumor infiltrating lymphocytes (TILs).
The data announced in patient-derived pancreatic ductal adenocarcinoma organoid model builds upon data announced in September 2022, which demonstrated that N-LIfT cell therapy showed tumor destruction across five different solid tumor types in PDX tumoroid models, and data announced in March 2022, which showed that N-LIfT showed potent tumor cell killing in a lung tumoroid model with significant superiority over current standards of care.
The current data builds on what the company said was a major breakthrough earlier this year, when it announced preclinical data demonstrating that its immunomodulatory alpha neutrophil product possesses both cytotoxic and immunomodulatory functionalities.